Synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones

An efficient method for the synthesis of novel 3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones from various 2-dimethylaminomethylidenecyclohexane-1,3-diones, (1,3-thiazol-2-yl)acetonitriles, and dimethylformamide dimethyl acetal was developed. These transformations proceeded through intermediate 2-[2-(4-aryl-1,3-thiazol-2-yl)-2-cyanoethenyl]-3-oxocyclohex-1-en-1-olates. They were isolated as piperidinium salts and used in further heterocyclization reactions with aromatic amines, giving novel 1-aryl-3-(1,3-thiazol-2-yl)-7,8-dihydroquinoline-2,5(1H,6H)-diones. These compounds were also obtained by preparative three-step “one pot” synthesis under controlled microwave irradiation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 412–417, February, 2008.     

Methyl (<Emphasis Type="Italic">Z</Emphasis>)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate: Synthesis and reactions with dimethyl malonate and methyl acetoacetate

Bromination–dehydrobromination of methyl (E)-3-(4-methylbenzenesulfonyl)prop-2-enoate gave methyl (Z)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate whose structure was determined by X-ray analysis. Methyl (Z)-3-bromo-3-(4-methylbenzenesulfonyl)prop-2-enoate behaved as a synthetic equivalent of methyl 3-(4-methylbenzenesulfonyl)prop-2-ynoate in reactions with dimethyl malonate and methyl acetoacetate, which afforded the corresponding Michael adducts, trimethyl 3-(4-methylbenzenesulfonyl)prop-1-ene-1,1,2-tricarboxylate and dimethyl (Z)-2-acetyl-3-(4-methylbenzenesulfonyl)but-2-enedioate, respectively, via nucleophilic attack on the β-position with respect to the sulfonyl group.     

Synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones by the condensation of cyclohexanone derivatives with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one

The synthesis of 1H-pyrazolo[3,4-c]isoquinolin-1-ones was carried out by reacting 3-aryl(heteryl)-2,4-diacetyl-5-hydroxy-5-methylcyclohexanones with 3-amino-1-phenyl-1H-pyrazol-5(4H)-one. The structure of the 7-acetyl-2,4,6,7,8,9-hexahydro-8-hydroxy-5,8-dimethyl-2-phenyl-6-(fur-2-yl)-1H-pyrazolo[3,4-c]isoquinolin-1-one obtained was proved by X-ray diffraction analysis.     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

DFT studies on tautomeric preferences of 1-(pyridin-2-yl)-4-(quinolin-2-yl)butane-2,3-dione in the gas phase and in solution

Density functional theory (DFT) calculations show that in vacuum such α-diketone as 1-(pyridin-2-yl)-4-(quinolin-2-yl)butane-2,3-dione is much less stable than its enolimine–enaminone ((1Z,3Z)-3-hydroxy-4-(pyridin-2-yl)-1-(quinolin-2(1H)-ylidene)but-3-en-2-one) and dienaminone tautomers ((1Z,3Z)-1-(pyridin-2-yl)-4-(quinolin-2-yl)buta-1,3-diene-2,3-diol). Other its tautomers (multiple basic and acidic centers in their molecules enable multiple proton transfer to take place) are even more labile. Strength of the intramolecular hydrogen bonds and aromatic character of the (quasi)rings [proved by the Harmonic Oscillator Model of Aromaticity (HOMA) index] in their molecules were found to be responsible for the observed tautomeric preferences. Polar and basic solvent disfavors and favors the enolimine and enaminone tautomers, respectively.     

Synthesis of stereoisomeric 4-(2-methylindolin-1-yl)- and 4-(2-methylindol-1-yl) derivatives of glutamic acid

The reaction of dimethyl (2S,4RS)-N-phthaloyl-4-bromoglutamate with 2-methylindoline afforded diastereomeric 4-(2-methylindolin-1-yl)-(S)-glutamic acid derivatives, whose oxidation gave rise to 4-(2-methylindol-1-yl)-(S)-glutamic acid derivatives.     

Synthesis and characterization of polymeric triphenyltin and cyclotetrameric tricyclohexyltin 2-(1H-imidazol-1-yl)acetates

The reaction of 2-(1H-imidazol-1-yl)acetic acid with (Ph₃Sn)₂O or Cy₃SnOH (Cy?=?cyclohexyl) yields triphenyltin 2-(1H-imidazol-1-yl)acetate (1) and tricyclohexyltin 2-(1H-imidazol-1-yl)acetate (2), respectively. 2-(1H-imidazol-1-yl)acetates in these two complexes show remarkably different coordination modes. Complex 1 forms a polymeric chain structure through intermolecular Sn–N interactions, while 2 displays a 28-membered macrocyclic tetranuclear structure by the assembly of Sn–N coordination bonds.     

Synthesis and anticancer activity of some novel diethyl {(chromonyl/pyrazolyl) [(4-oxo-2-phenyl-quinazolin-3(4H)-yl)amino]methyl}phosphonates

Abstract

The synthesis of some novel chromonyl and pyrazolyl α-aminophosphonates containing a quinazolinone ring was carried out by applying Pudovik and Kabachnik-Fields reactions under solvent- and catalyst-free conditions. The anticancer activities of these compounds were evaluated against five cancer cell lines. 3-{[(3-Phenyl/1,3-diphenyl-1H-pyrazol-4-yl)methylidene]amino}-2-phenyl-quinazolin-4(3H)-ones (3d,e) and diethyl {[3-phenyl/1,3-diphenyl-1H-pyrazol-4-yl][(4-oxo-2-phenyl-quinazolin-3(4H) yl)amino] methyl}phosphonates (4d,e) displayed the potent anticancer activities against HCT116, MCF-7 and HepG2 cell lines in comparison with the standard drug.     

Reaction Between Alkyl Isocyanides and Cyclic 1,3-Diketones: A Convenient Synthesis of Functionalized 4 H-Pyrans

Alkyl isocyanides react with dialkyl acetylendicarboxylates in the presence of CH-acids such as cyclopentane-1,3-dione, cyclohexane-1,3-dione, or 5,5-dimethylcyclohexane-1,3-dione to afford highly functionalized 4H-pyrans in fairly high yields. In the case of reaction between dimethyl acetylenedicarboxylate and 5,5-dimethylcyclohexane-1,3-dione in the presence of cyclohexyl isocyanide or benzyl isocyanide tetrahydro-cyclopenta[b]pyran derivatives were isolated in addition to the 4H-pyran system. The free energy barrier (96.9kJmol^–1) for restricted rotation around the polarized double bond of the enaminone moiety in dimethyl 2-[cyclohexylamino-(4,4-dimethyl-2,6-dioxocyclohexylidene)methyl]but-2-enedioate was determined by dynamic NMR spectroscopy.     

A new method for the synthesis of 6H,11H-indolo[3,2-c]-isoquinolin-5-ones/thiones and their reactions

The synthesis of 8-substituted and unsubstituted 6H,11H-indolo[3,2-c]isoquinolin-5-ones/thiones 3a-c and 4a-c and their derivatives viz, ethyl (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetates 5a-c , (8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)acetyl hydrazides 6a-c , 3,5-disubstituted-pyrazoles 7a-c and 8a-c , 3-substituted-pyrazol-5-ones 9a-c and 5-(8-substituted-6H,11H-indolo[3,2-c]isoquinolin-5-on-6-yl)methyl-1,3,4-oxadiazole-2-thiones 10a-c , also ethyl (8-substituted-11H-indolo[3,2-c]isoquinolin-5-ylthio)ace-tates 11a-c , (8-substituted-11Hindolo[3,2-c]isoquinolin-5-ylthio)acetyl hydrazides 12a-c , 3,5-disubstituted-pyrazoles 13a-c and 14a-c , 3-substituted-pyrazol-5-ones 15a-c and 5-(8-substituted-11H-indolo[3,2-c]isoquin-olin-5-yl)thiomethyl-1,3,4-oxadiazole-2-thiones 16a-c is described.     

Synthesis, characterization, and biological activities of some transition metal(II) complexes with the thiosemicarbazone derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one

A new 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one thiosemicarbazone (HL) was synthesized derived from 4-[1-(4-methylphenylsulfonyl)-1H-indol-3-yl]but-3-en-2-one. Four transition metal(II) complexes of HL have been prepared. Elemental analysis, molar conductivity, IR, UV, ¹H NMR spectra, and TG-DTA have been used to characterize these complexes. The complexes have the general formula ML₂, where M = Zn, Cu, Co, and Ni. The ligand and its complexes have been studied for their possible biological activity including anti-inflammatory, antibacterial, and antitumour activity in vitro.     

BF3·Et2O catalyzed intramolecular cyclization of diethyl 2-(dialkoxyphosphorylethynyl)-2-arylaminomalonates to 3-phosphonylated indoles

The boron trifluoride diethyl etherate catalyzed intramolecular cyclization of diethyl 2-(dialkoxyphosphorylethynyl)-2-arylaminomalonates afforded a series of novel 3-phosphonylated indoles, diethyl 2-[3-(dialkoxyphosphoryl)-1H-indol-2-yl]propanedioates. Decarboxylation of the latter compounds resulted in the formation of ethyl 2-[3-(dialkoxyphosphoryl)-1H-indol-2-yl]acetates.     

Reaction Between Alkyl Isocyanides and Cyclic 1,3-Diketones: A Convenient Synthesis of Functionalized 4<Emphasis Type="Italic">H</Emphasis>-Pyrans

Summary. Alkyl isocyanides react with dialkyl acetylendicarboxylates in the presence of CH-acids such as cyclopentane-1,3-dione, cyclohexane-1,3-dione, or 5,5-dimethylcyclohexane-1,3-dione to afford highly functionalized 4H-pyrans in fairly high yields. In the case of reaction between dimethyl acetylenedicarboxylate and 5,5-dimethylcyclohexane-1,3-dione in the presence of cyclohexyl isocyanide or benzyl isocyanide tetrahydro-cyclopenta[b]pyran derivatives were isolated in addition to the 4H-pyran system. The free energy barrier (96.9kJmol^–1) for restricted rotation around the polarized double bond of the enaminone moiety in dimethyl 2-[cyclohexylamino-(4,4-dimethyl-2,6-dioxocyclohexylidene)methyl]but-2-enedioate was determined by dynamic NMR spectroscopy.     

5-phenyl-2H-tetrazol-2-ylmethyl ketones in the synthesis of tetrazolylalkanols and tetrazolyl(hydroxy)alkylphosphonates

The reduction of 1-(5-phenyl-2H-tetrazol-2-yl)propan-2-one and 1-phenyl-2-(5-phenyl-2H-tetrazol-2-yl)ethanone with sodium tetrahydridoborate gave 1-(5-phenyl-2H-tetrazol-2-yl)propan-1-ol and 1-phenyl-2-(5-phenyl-2H-tetrazol-2-yl)ethanol, respectively. Only 1-(5-phenyl-2H-tetrazol-2-yl)propan-2-one was reduced with baker’s yeast with an appreciable yield. 1-(5-Phenyl-2H-tetrazol-2-yl)propan-2-one and 1-phenyl-2-(5-phenyl-2H-tetrazol-2-yl)ethanone reacted with diethyl phosphonate in the presence of potassium fluoride to produce the corresponding diethyl [hydroxy(5-phenyl-2H-tetrazol-2-yl)alkyl]phosphonates.     

Chemistry of iminofurans: X. Synthesis and hydrolysis of 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

5-Aryl(hetaryl)furan-2,3-diones reacted with N-(triphenyl-λ⁵-phosphanylidene)-4,5,6,7-tetrahydro-1-benzothiophen-2-amines to give 5-aryl(hetaryl)-2-[(4,5,6,7-tetrahydro-1-benzothiophen-2-yl)imino]furan-3(2H)-ones whose acid hydrolysis afforded 4-aryl(hetaryl)-2-hydroxy-4-oxo-N-(4,5,6,7-tetrahydro-1-benzothiophen- 2-yl)but-2-enamides.     

Facile one pot multicomponent synthesis of novel 4-(benzofuran-2-yl)-2-(3-(aryl/heteryl)-5-(aryl/heteryl)-4,5-dihydro-1H-pyrazol-1yl)thiazole derivatives

An efficient base catalyzed one pot multicomponent reaction of aryl/hetryl chalcones, thiosemicarbazide and 1-(benzofuran-2-yl)-2-bromoethan-1-one was developed to synthesize the novel 4-(benzofuran-2-yl)-2-(3-(aryl/heteryl)-5-(aryl/heteryl)-4,5-dihydro-1H-pyrazol-1yl)thiazole derivatives.     

Diels-alder reaction of (E)-4-(2-nitroethenyl)-1H-imidazoles and methyl (E)-3-(1-imidazol-4-yl)propenoates

Diels-Alder reaction of methyl (E)-3-(1H-imidazol-4-yl)propenoates 2, 3a-c and (E)4-(2-nitroethenyl)-1H-imidazoles 3d,e with 2,3-dimethyl-1,3-butadiene, cyclopentadiene, and cyclohexa-1,3-diene gave the corresponding cycloadducts 6–9 .     

Simple procedure for preparation of quinoxalin-2(1H)-one 3-[Oxo(cyclo)alkyl(idene)] derivatives

A simple preparative procedure was developed for 3-(2-oxoalkylidene)-3,4-dihydroquinoxalin-2(1H)-ones, 4,5-dihydroxy-1-[3-oxo-3,4-dihydroquinoxalin-2(1H)-ylidene]-3,5-octadiene-2,7-dione, and 3-(2,3-dihydroxy-4-methyl-5-oxo-1,3-cyclopentadien-1-yl)quinoxalin-2(1H)-one by reaction of methyl ketones first with diethyl oxalate in the presence of sodium, and then with o-phenylenediamine.     

Halocyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1<Emphasis Type="Italic">H</Emphasis>-benzo[<Emphasis Type="Italic">de</Emphasis>]isoquinoline-1,3(2<Emphasis Type="Italic">H</Emphasis>)-dione

Cyclization of 2-(2-{4-[allylamino(thioxo)methyl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione by the action of iodine, bromine, or sulfuryl chloride gave 2-(2-{4-[4,5-dihydro-5-(halomethyl)-thiazol-2-yl]piperazin-1-yl}ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione hydrohalides which were converted into 2-{2-[4-(5-methylthiazol-2-yl)piperazin-1-yl]ethyl}-1H-benzo[de]isoquinoline-1,3(2H)-dione.     

Oxidation of N-acyl-2-(cycloalk-1-enyl)anilines with ozone and hydrogen peroxide

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH₄ gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me₂S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H₂O₂ in HCOOH affords -(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H₂O₂ in the presence of Na₂WO₄ and H₃PO₄ gives 3,1-benzooxazine in high yield.